Project Description

Lactose intolerance is a prevalent issue in our world that cannot be overlooked. As much as 65% of the world’s human population is intolerant to ingested dietary lactose. The problem is even more severe in certain ethnic groups. The lactose intolerance rate for Asians, for example, is as high as 70%. This rate goes up to almost 100% in African populations. [1] Lactose intolerance can be developed at any age, even well into adulthood. People with lactose intolerance suffer from bloating, diarrhea, and gas due to their inability to digest lactose in dairy products. [1] Being lactose intolerant not only means that patients cannot indulge in foods such as yogurt and ice cream, but a lack of dietary intake also causes detrimental health effects. It may lead to nutrient deficiency that can increase the body’s risk for osteoporosis and other bone diseases. [2]

Demographics of the lactose intolerance rate across the world [10]

Current solution:

Unfortunately, after intensive market research, we found that alternatives to dairy products for lactose intolerant people such as lactose-free milk and lactase drops are expensive and inaccessible to many. Available probiotics and prebiotic used to treat lactose intolerance also have weak survivability. Their effectiveness is hindered mainly by the fact that the bacteria cannot successfully pass through the stomach and reach the duodenum while maintaining a stable population. [3]

Based on these findings, we came up with a synbio approach to alleviate and potentially cure lactose intolerance.

Our solution:

We plan to use a simple three step process to create this potential cure. We will firstly find a chassis suitable for the job and tailor its genetics to produce lactase. We will then find a way to safely transplant the chassis to the patient’s small intestines. We will lastly ensure that the chassis survives and functions effectively in the intestinal environment in the long term. As a result, the chassis would be able to produce the enzymes needed to catalyze the breakdown of lactose there and then in the patient’s abdomen.

Firstly, we decided to use Escherichia coli strain Nissle 1917 as our chassis. E. coli has been the most popular chassis strand with high productivity and maneuverability. Its Nissle 1917 strain, originally discovered in the feces of German Soldiers during the First World War, is a widely used chassis for gastro-intestinal treatment. [4] We aim to use this strand of E. coli to produce β-galactosidase LacZ in the small intestines, an enzyme that can effectively breakdown lactose into glucose and galactose, both degradable by the human digestive track. [5] The produced enzymes will be transported to the extracellular environment through a signal peptide. [6] This makes sure that the bacteria themselves won’t ingest the lactose to produce gasses, effectively stopping all forms of bloating, discomfort or diarrhea.

The structure of β-galactosidase LacZ [11]

Second, we plan to use enteric coated pills to contain the freeze-dried bacteria for ingestion. When swallowed, enteric coated pills do not dissolve in the stomach like normal pills would, but only starts to break down in the small intestine. [7] This helps the bacteria bypass the chemical barrier the gastric acid imposes and ensures a safe transport to the intestines.

Third, we aim to create a protective film using CAP, capsular polysaccharides surrounding Escherichia coli strain Nissle 1917, to ensure that the bacteria safely implants itself in the intestinal environment without damage. [8] The gene for the CAP will be encoded in the bacteria so it will be spontaneously produced. The CAP helps the bacteria adapt to a wider range of temperature and pH, shuts out harmful chemicals and toxins, as well as assisting them to stick to the intestinal wall. [9]

The production and internal structure of CAP [8]